Structural characterization of the intra- and inter-repeat copper binding modes within the N-terminal region of "prion related protein" (PrP-rel-2) of zebrafish.
The unique biology of prion proteins (PrPs) allied with the public-health risks posed by prion zoonoses, such as various animal neurodegenerations, has focused much attention on the molecular basis of the controls cross-species and on the similarities between PrPs from different species. Given the common feature of PrPs as Cu(2+) binding proteins, it appears relevant to compare the impact of Cu(2+) on the stability constants and structures of "physiological" complexes. After having comprehensively delineated the interaction of Cu(2+) with mammalian and avian PrPs, the stabilities and molecular structures of species generated by Cu(2+) interacting with the irregular repeated domain derived from Danio rerio zebrafish PrP-rel-2 were investigated. Copper complexes with different zebrafish PrP-rel-2 fragments were analyzed by potentiometric and spectroscopic techniques. The data were interpreted as to provide evidence of all investigated repeat units selectively binding Cu(2+) via the His imidazole(s). The structural models obtained from paramagnetic NMR showed an intra- or inter-copper binding according to the number of the His in the sequence. In comparison to the mammalian and avian cases, the enzymatic function referred to SOD-like activity was shown to be rather faint in the fish PrPs cases.
Gaggelli
Elena
E
Department of Chemistry, University of Siena, Siena, Italy.
Jankowska
Elzbieta
E
Kozlowski
Henryk
H
Marcinkowska
Alina
A
Migliorini
Caterina
C
Stanczak
Pawel
P
Valensin
Daniela
D
Valensin
Gianni
G
D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D003300:Copper / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011328:Prions / Q000737:chemistry* / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D015027:Zebrafish
D011328:Prions; D003300:Copper